Presenilin-1 controls glucose metabolism and identity of pancreatic beta cells
Koshenov, Z.; Postic, S.; Schosiwohl, G.; van Amsterdam, S.; Hois-Zelinka, V.; Oflaz, F. E.; Rost, R.; Tiapko, O.; Gottschalk, B.; Hirtl, M.; Bachkoenig, O. G.; Koshenova, A.; Erdogan, Y. C.; Sagintayev, A.; Krnjic, A.; Pfabe, J.; Sarikas, S.; Hochreiter, B.; Gindlhuber, J.; Schittmayer, M.; Tadic, J.; Ehall, B.; Madeo, F.; Madl, T.; Malli, R.; Birner-Gruenberger, R.; Pieber, T.; Eisenberg, T.; Slak Rupnik, M.; Graier, W. F.
Show abstract
AbstractPresenilin 1 is an endoplasmic reticulum protein, most known for its role in pathogenesis of familial Alzheimers Disease (AD). Presenilin 1 has been attributed roles in intracellular calcium homeostasis in the brain, as well as in the pancreatic beta cells, where it has been shown to be fundamental for glucose-induced insulin secretion. Functional similarity of presenilin 1 in regulation of intracellular calcium homeostasis in the brain and pancreas prompted us to investigate a prevalent assumption that associates AD and diabetes mellitus. By examining pancreatic islets from AD model mice, we have found deficits in initial phase of glucose-induced calcium signaling and insulin secretion. Furthermore, these transgenic mice showed a tendency towards reduced expression of mature beta cell markers, which was even more pronounced in islets and beta cell lines with a transient knock down of presenilin 1. We demonstrate here that presenilin 1 controls beta cell glycolysis by regulating sub-cellular calcium homeostasis and, in doing so, contributes to preservation of beta cell identity.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Target deconvolution of an insulin hypersecretion-inducer acting through VDAC1 with a distinct transcriptomic signature in beta-cells 95%
- Arid1a loss potentiates pancreatic β-cell regeneration through activation of EGF signaling 94%
- Chronic intermittent fasting impairs β-cell maturation and function in adolescent mice 94%
Similar papers in this journal
- Signal transduction pathways controlling Ins2 gene activity and β cell state transitions 94%
- Multiplexed CRISPR gene editing in primary human islet cells with Cas9 ribonucleoprotein 94%
- Islet macrophages shift to a reparative state following pancreatic beta-cell death and are a major source of islet IGF-1 93%
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.